The present invention relates to compounds which have been found to exhibit anti-acetylcholinesterase activity and/or inhibition of 5-HT uptake and/or inhibition of noradrenaline uptake. More specifically, the invention concerns polycyclic compounds and analogues thereof, methods for their preparation, pharmaceutical formulations containing them and their use as neurotransmitter potentiating agents, in particular in the treatment of symptoms of Alzheimer's disease.
Much work has been done in research in the area of drugs affecting neurotransmitter systems in the central nervous system (CNS). Neurotransmitter molecules are involved in rapid communication in the normal CNS and in pathologic conditions of the CNS. Most of the drugs available to the psychiatrist or neurologist for the treatment of CNS disease function by affecting neurotransmitter pathways directly or indirectly. Of all the CNS disorders known to date, those associated with organic or degenerative dementia are not able to be treated effectively with the range of drugs currently available. A particular disorder, Alzheimer's disease, also known as degenerative dementia, senile dementia, senile dementia of the Alzheimer type and organic brain syndrome, has no known effective treatment therefor.
Certain drugs, such as so-called centrally active muscarinic drugs (i.e. drugs which act directly on the acetylcholine receptors to produce a response), act on so-called muscarinic receptors. Muscarinic receptors have been found to be made up of at least 3 subclasses: M.sub.1, M.sub.2 and M.sub.3. These receptors are found in the brain, heart and gut, and as a result, the use of muscarinic drugs carries with it the possibility of undesirable side effects such as nausea or slowing or stopping of the heart.
Tacrine, a tricyclic acetylcholine esterase inhibitor is known to produce liver damage as a side effect, which, although not believed to be irreversible in nature, is nevertheless undesirable.
There exists a need to provide more effective drugs for the treatment of, or alleviation of symptoms of organic or degenerative dementia diseases of the CNS.